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Smads mediate signaling of the TGFβ superfamily in normal keratinocytes but are lost during skin chemical carcinogenesis

Oncogene volume 20, pages 471–483 (2001)Cite this article

Abstract

The Smads are the signaling mediators of the TGFβ superfamily. In the present study, we examined Smad expression in mouse epidermis and chemically-induced skin tumors. Mutations in Smad2 and -4 genes were also screened. Transcripts of Smad1 through -5 were constantly expressed in the epidermis regardless of changes in TGFβ signaling, state of differentiation and stages of carcinogenesis. Smad7 transcripts were barely detectable in keratinocytes, but were induced by TGFβ1 treatment and in chemically-induced skin tumors. At the protein level, Smad1 was detected throughout the epidermis, whereas Smad2 through -5 exhibited greater levels in suprabasal layers than basal keratinocytes. In cultured keratinocytes, Smad2, -3 and -4 underwent nuclear translocation upon TGFβ1 treatment. Furthermore, nuclear translocation of Smads correlated with decreased BrdU labeling in proliferative keratinocytes. Although no mutations were detected in the Smad2 and -4 genes in tumors, proteins of Smad1 through -5 were partially or completely lost in carcinomas. These data document that Smads are expressed at high levels in the epidermis and mediate signaling of the TGFβ superfamily. During skin carcinogenesis, loss of Smad1 through -5 and overexpression of Smad7 may contribute to the loss of growth inhibition mediated by TGFβ superfamily members, thus resulting in tumor progression.

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Acknowledgements

The authors would like to thank Dr Dennis R Roop, Dr Kristin M Liefer and Dr Rebekah L Waikel for their critical comments on the manuscript. Ms Ping Li, Miss Dongyan Wang and Mrs Mattie Brooks provided excellent technical assistance. This work was supported by NIH grants CA79998 and CA 87849 to X-J Wang.

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Authors and Affiliations

  1. Department of Dermatology, Baylor College of Medicine, Houston, TX 77030, Texas, USA

    Wei He, Daniel A Smith, Todd E Myers & Xiao-Jing Wang

  2. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, Texas, USA

    Tongyu Cao & Xiao-Jing Wang

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He, W., Cao, T., Smith, D. et al. Smads mediate signaling of the TGFβ superfamily in normal keratinocytes but are lost during skin chemical carcinogenesis. Oncogene 20, 471–483 (2001). https://doi.org/10.1038/sj.onc.1204117

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